Neurodegenerative disorders mean a gradually structural and functional loss of a nerve cell (neuron). They usually affect a particular part of the nervous system, accompanying the symptoms such as dementia, extrapyramidal disease, cerebellar disorder, dysesthesia or dyskinesia. The complex symptoms may be shown when affecting the various parts at the same time. A diagnosis is gotten by a patient's clinical sign. However, the diagnosis in this case is difficult to make because it shows multiple symptoms and the varied diseases have the common clinical signs. (Soc. Sci. Med. Vol. 40. No. 6, pp. 847-585, 1995).
Signs of the onset of neurodegenerative disorders appear gradually and mostly occur with aging. Once an outbreak, neurodegenerative disorders progress for several years or decades until death. It is known that the genetic effects according to a family history are considerable. According to the clinical symptoms, degenerative disorders are classified into paralytic dementia (Alzheimer's disease etc.), neurologic disorder (Pick's disease etc.), abnormalities in posture and exercise (Parkinson's disease etc.), progressive ataxia, muscular atrophy and weakness, and sensation and movement disorders. (International Journal of Engineering and Technology, Vol. 2, No. 4, Aug. 2010 Classification of Neurodegenerative Disorders Based on Major Risk Factors Employing Machine Learning Techniques).
In 1980s, it was raised that neurotrophic factors have the potential to treat neurodegenerative disorders as Alzheimer's disease experiment (Nature. 1987 Sep. 3-9; 329(6134):65-8. Amelioration of cholinergic neuron atrophy and spatial memory impairment in aged rats by nerve growth factor) The loss of neuron of basal forebrain by aging known as Alzheimer's disease is recovered by administration of nerve growth factor (NGF) to the lateral ventricle of the brain. As the memory improvement of tested animals is reported, the studies for treating neurodegenerative disorders are conducted by using neurotrophic factor. It met with a good result that the function of motor neurons damaged by Brain-derived neurotrophic factor (BDNF), Neurotrophin-3 (NT-3), Neurotrophin-4 (NT-4), and Ciliary neurotrophic factor (CNTF) as neurotrophic factor family is recovered in the study after hurting the function of the motor neurons by sectioning the facial nerves and the sciatic nerves as the follow-up study. (Nature. 1992 Dec. 24-31; 360(6406):757-9. Brain-derived neurotrophic factor prevents the death of motor neurons in newborn rats after nerve section.). In the experiment used gene recombination mice (wobbler) which suffered from losing its motor neurons and function gradually, the function was enhanced by administrating BDNF and CNTF to increase the number of motor neurons. (Science. 1994 Aug. 19; 265(5175):1107-10. Arrest of motor neuron disease in wobbler mice cotreated with CNTF and BDNF). Besides the said experiments, neurotrophic factors increase neurons and their function in the pathological model of motor neurons and various senses, so it showed the improvement of disorder related to memory, perception, and behavior in the laboratory animals.
Based on the results of pre-clinical experiments, there were trials to apply neurotrophic factor for the treatment of Lou Gehrig's disease in 1990s. Lou Gehrig's disease is a degenerative nervous disease which only motor neurons die out selectively and makes human die due to the dysfunction of respiratory organs with paralysis of the whole body. BDNF was hypodermically or subarachnoidally administered, however, a pain of injection region and the side effect of digestive system was shown. So, there had been no choice but to administer the smaller amount of BDNF than the pre-clinical experiment. As a result, the regeneration and improvement of motor neuron and its function had minimal effect. (Exp Neurol. 1993 Nov.;124(1):64-72. Review. Experimental rationale for the therapeutic use of neurotrophins in amyotrophic lateral sclerosis). Similarly, symptoms such as a fever, a pain of injection region or a loss of appetite which were more severe adverse reactions than the case of administration of BDNF were shown when CNTF was injected to the patient suffered from Lou Gehrig's disease, therefore CNTF was administered with a limited amount. As a result, the regeneration and improvement of motor neuron and its function was insignificant. (Neurobiol Aging. 1994 Mar.-Apr.; 15(2):249-51. Review Neurotrophic growth factors and neurodegenerative diseases: therapeutic potential of the neurotrophins and ciliary neurotrophic factor). The method of having neurotrophic factor such as BDNF, CNTF, etc as a form of the recombinant protein reach the central and peripheral nervous system by injecting in vivo had the limited amount of injecting protein. In case of the experiment which attempted to treat the patient having Alzheimer's disease using NGF, it couldn't show the significant result since there were side effects, the limit of injecting amount, the drug delivery and uncertain pharmacodynamics.
Although a disappointing result of the clinical experiment, there have been many experimental evidences which are possible to treat neurodegenerative disorders using neurotrophic factors. Typically, in case of Huntington's disease, which its symptoms are abnormal movements, personality changes, decreased cognitive ability, and early death due to increasing poly Q in Huntington protein, a lot of studies noted BDNF as a main target of abnormal Huntington protein. This theory was supported by decreasing the amount of BDNF in the striatum of the pathological laboratory animals and the patient having Huntington's disease. (Science. 2001 Jul. 20;293(5529):493-8. Epub 2001 Jun. 4 Loss of Huntington-mediated BDNF gene transcription in Huntington's disease).
By the way, when the method to administer neurotrophic factor hypodermically or subarchnoidally in vivo with the form of a recombinant protein as same as the existing method in order to treat degenerative disorders was chosen, decreasing the amount of administration and reducing its effect were repeated due to the side effect. Therefore the studies of neurotrophic factor enhancer which is indirect way to increase the amount of neurotrophic factor biosynthesized itself in vivo in 2000s. (Hum Gene Ther. 1999 Dec. 10;10(18):2987-97. Brain-derived neurotrophic factor-mediated protection of striatal neurons in an excitotoxic rat model of Huntington's disease, as demonstrated by adenoviral gene transfer).
Dioscorea Rhizoma, a plant belonging to Dioscoreaceae, is the teIin for fresh rhizome of Dioscorea batatas Decaisne or Dioscorea japonica Thunberg, void of periderm, or for that obtained after the fresh rhizome was steamed and dried in the herbal medicine. It is widely distributed in Korea, China, and Japan, and was used as a medicine. It has remedial effects on tonic nutrition, digestive disorders, diabetes, cough, pulmonary disease, strengthening kidney function, etc and toxicity and side effects often have not released. Moreover, Dioscorea nipponica is a rhizome of Dioscorea nipponica Makino, a climbing perennial plant of Dioscoreaceae. It is widely distributed in Korea, China, and Japan, and was used as a medicine. It has effects on better circulation of blood, loosening the muscles, removing indigestion, keeping one's urine open, removing sputum, and prevention of malaria paroxysm and toxicity and side effects often have not released.
Korean Patent No. 854621 provides a composition for the prevention and treatment of peripheral neuropathy, comprising an extract from a plant selected from among Dioscorea nipponica, Dioscorea quinqueloba, Dioscorea batatas, Dioscorea japonica and Dioscorea tokora, disclosing that the composition induces the growth of neurites and increases the secretion of endogenous nerve growth factor, thus being effective for preventing or treating peripheral neuropathy.
The present inventors confirmed that the function of the extract from a plant selected from among Dioscorea nipponica, Dioscorea quinqueloba, Dioscorea batatas, Dioscorea japonica and Dioscorea tokora was to induce the significant growth of neurites and to increase the secretion of endogenous NGF as disclosed in Korean Patent No. 854621. Based on that, the present invention has been completed after ascertaining that Dioscorea Rhizoma and Dioscorea nipponica in the selectively particular ratio show very significant synergism although the said herbs each or their mixed herb extracts surprisingly induce almost same growth of neurites as well as increase the secretion of endogenous nerve growth factor while studying a herb extract which has effects on neural cell proliferation, promotion of neuritis formation and enhancing cognitive abilities by increasing the contents of nerve growth factor in the laboratory animals in vivo.